Because dry eye is so prevalent among contact lens wearers, eyecare
practitioners must stay up to date with the latest research and the newest
products. Here�s where we stand today.

By Jason J. Nichols, OD, MPH, PhD, FAAO

Dry eye disease seems ubiquitous these days. Some 12 to 15 million Americans who
don�t wear contact lenses have dry eye symptoms, and as many as 50% of contact
lens wearers suffer from this condition as well.1

The scientific and clinical understanding of tear film physiology and its
relationship to dry eye disease is continually changing as research into the
etiology and disease course advances and as manufacturers introduce new targeted
therapies. These new directions in research, understanding and product
development can leave our heads spinning.

In the contact lens field, terms such as wettability, lubriciousness, friction,
modulus and tribology are being used frequently to characterize new polymers and
their corresponding lenses, but with little qualification or standardization of
the methods for studying or interpreting each.

This article will update you on the latest information on dry eyes and contact
lens wear to help you stay current when caring for your patients.

Impact of Dry Eye

Most contact lens practitioners understand the all-to-common dry eye symptoms
that their patients experience. We know contact lens wearers experience ocular
irritation much more frequently than non-lens wearers do.1 In a recent study1,
my colleagues and I found that 52.3% of contact lens wearers were classified as
having dry eyes based on self-reporting various symptoms, while about 24% of
spectacle wearers and only 7% of clinical emmetropes had the same level of
symptoms. In other words, lens wearers were about 12.5 times more likely than
clinical emmetropes and five times more likely than spectacle wearers to
experience dry eyes.

Another important consideration is how symptoms increase in contact lens wearers
during the day. This could prove to be a critical assessment in terms of
prescribing a material (or material/care system combination) that improves
comfort levels so patients can wear their lenses longer. Our ultimate goal is to
keep patients safely and comfortably wearing contact lenses for as long as they
desire, and this relates in large part to their daily comfort levels.

In another recent study,2 my colleagues and I found that out of 730
subjects surveyed, more than one-half (n = 453, 62%) had some experience with
wearing contact lenses. Of those with some experience, 26% (n = 119) reported
that contact lenses were not the ideal form of correction for them, while
another 24% (n = 109) had discontinued wearing contact lenses permanently.

When comparing the groups studied (current satisfied lens wearers, current
dissatisfied lens wearers and dropouts), we learned the dissatisfied lens
wearers tended to be female, while those who discontinued lens wear tended to be
male. Furthermore, former lens wearers were likely to have tried both rigid and
soft lens modalities and spent less total time in lenses than current lens
wearers (about 3 to 4 years less on average).

The study also showed that a patient�s age when starting contact lens wear was a
significant determinant of future satisfaction and continuation with lens wear.
We found that the younger a patient is when first fitted with contact lenses,
the more likely he is to be satisfied with them and the less likely he is to
discontinue wearing them. This is critical information that we can use in
practice to help keep our patients happy and successful.

Last, and not surprising, the most frequently reported reason for
dissatisfaction with or discontinuation of lens wear was ocular surface-related
symptoms. The two studies outlined here help to define the concern relative to
improving our patients� experiences with contact lenses.

In 1993 and 1994, the National Eye Institute and key corporations sponsored
workshops on dry eye syndrome. A 1995 report generated from theseworkshops
indicated that contact lens-related dry eye is a subclassification of dry eye
syndrome, yet the epidemiology and etiology of this condition still elude us.3
Contact lens-related dry eye was termed evaporative relative to its etiology,
although no studies have directly compared evaporation rates in satisfied lens
wearers to rates in patients with contact lens-related dry eyes.

The next few sections of this article will explore this evaporative mechanism as
well as the characteristics of contact lens materials that may be associated
with patient comfort and preference. To this point, the mechanism of contact
lens-related dry eye and comfort is poorly understood and in need of further
study. Knowledge of the disease mechanism may allow clinicians to offset any
potential for discomfort, ocular surface desiccation and disease, which could
lead to failure of contact lens wear in these patients.

It is important that we move past incremental improvements in both lens
materials and care solutions; to do this, the industry must continue to fund
basic, fundamental research into understanding disease mechanisms so new
materials and solutions can be identified to prevent or stop the disease
process.

Lens Material Considerations

There have been tremendous advances in polymer chemistry over the last 5 to 7
years, and our patients are benefiting on several fronts. Silicone hydrogels
have brought much-needed increases in oxygen permeability, and other
characteristics of some silicone hydrogel materials seem to improve comfort.

More recently, wetting agents have been incorporated into daily disposable
materials to improve performance and comfort. To understand the interaction
between contact lenses and the tear film, we must first understand the surface
characteristics of polymers. Let�s review some fundamental concepts and
terminology as we continue the discussion about these novel materials.

� Wettability. Wettability relates to cohesive forces (forces within a molecule
of one component) and adhesive forces (forces between two different molecular
components). Specifically, cohesive forces tend to keep one component together
(e.g., water is attracted to itself), whereas adhesive forces must be
substantial enough to overcome cohesive forces for the surface to become wetted.

Within a drop of liquid, for
example, cohesive forces pull each molecule equally in all directions with
little to no net force. However, the surface of the liquid has excess energy
(surface energy or tension) because there is no outward force that can negate
the inward pulling forces of the molecules. The stronger the cohesive forces are
within the drop, the higher the surface tension. When a drop of liquid is in
contact with a solid surface (which has surface energy itself), energies at the
interface (interfacial tension) need to be considered as the liquid becomes
attracted to the solid surface, reducing the surface tension of the liquid.

In terms of the ultimate wettability of a system, we need to consider the
surface tension of the liquid, the surface tension of the solid surface and the
interfacial tension. High surface tension of the liquid (due to its own high
cohesive forces) and high interfacial tension (low adhesion forces) are
associated with decreased wettability, whereas lowering the surface tension of
the liquid or increasing the surface tension of the solid will lead to increased
wettability.

We measure wettability in vitro via contact angles. Several methods exist,
including the sessile drop, the captive bubble and the Wilhelmy balance methods.
Contact angles can be advancing or receding, and each may give you different
information about the system being evaluated. In general, lower contact angles
indicate more wettability, and a contact angle of zero indicates complete
wettability.

Historically, some doctors have been guarded about the clinical utility of
contact lens wettability measurements, given the in vitro nature of the data
obtained, particularly because there is very little information on how these
measurements relate to the subjective performance of various materials. However,
we are obtaining more clinically meaningful data by using newer approaches and
investigations.

One alternative approach is to determine the impact of wear on wettability by
measuring baseline (�out-of-the-box�) wettability followed by post-wear
wettability. This gives us insight into factors that influence wettability, such
as wearing time, care solutions and deposition. Figures 1, 2 and 3 are examples
of surface measurements of wettability, with Figure 1 showing the process of
measuring an advancing contact angle, while Figure 2 shows a very wettable
silicone hydrogel surface (note that the contact angle is 0�) and Figure 3
demonstrates a very unwettable silicone hydrogel lens surface (note that the
contact angle is around 90�).

Given the potential limitations of in vitro measurements, more in vivo surrogate
measurements of wettability are of clinical interest, and advances have been
made in this regard. Traditionally, we can approximate clinical wettability
measurements by measuring tear film stability and breakup. However, even this is
confusing in that we don�t really understand the outcome of the test. For
instance, with fluorescein-associated tear breakup, what is not clear when one
observes a �dry spot� is whether or not a tear film is present or if the dimming
is associated with quenching of fluorescence. Newer, noninvasive imaging
technologies, namely optical coherence tomography and interferometry, are
providing even more insight into on-eye tear film distribution, especially as it
relates to contact lens surfaces. While both technologies are still used mainly
for research, each is capable of providing tremendous insight into tear film
distribution, thickness and breakup. This information can help us understand
on-eye differences in polymers, care solutions, rewetting agents and various
other factors that influence the aforementioned tear-film parameters. Figures 4
to 6 show examples of a stable pre-lens tear film and images that show
particularly unstable pre-lens tear films, indicating breakup that may be due to
dewetting. (Note the difference in the images relative to the characteristics of
the dry spots.)

� Tribology. Tribology deals
with the design, friction, wear and lubrication of interacting surfaces in
relative motion. It�s gaining interest among those involved in contact lens
research, development and marketing. I want to emphasize that lubrication and
wettability are different characteristics, although they may be related.
Technically, lubrication occurs when otherwise adjacent surfaces are separated
by a film. There are at least two distinct types of lubricants: so-called
boundary lubricants, which offer incomplete separation of the surfaces; and
hydrodynamic lubricants, which offer complete separation of the surfaces.

Lubricants are used to reduce friction between two surfaces, and traditionally
they are oil-based (i.e., synthetic, mineral, natural). Clinically speaking,
lubrication is relevant when considering interaction between a contact lens and
the palpebral conjunctiva (say, during a blink) and also in terms of the
posterior surface of the contact lens and the cornea. It seems that it should be
important for lubricants to maintain wettability in order for them to coat a
surface.

Kinetic friction is the energy created when two surfaces are opposed in motion,
usually opposite in direction to the surface that is in motion. Friction is
classified using the coefficient of friction, which is a measure of the force
created between two surfaces. In general, rougher surfaces tend to have higher
coefficients of friction. However, the tear film-lens surface interface is
interesting relative to our understanding of friction.

Similar to the issues relating to measuring wettability in vitro, it is unclear
how measures of friction relate to on-eye performance differences associated
with lens surfaces. Certainly, it seems intuitive that we would want to reduce
the friction of the tear film-lens surface, but it could be likely that a stable
pre-lens tear film holds this responsibility. If we consider the supposedly
rough corneal glycocalyx and its role in maintaining a stable precorneal tear
film, we might logically surmise that a similarly structured contact lens
surface, which also would be considered inherently rough, would be better than
an inherently smooth surface in maintaining a stable pre-lens tear film. Many
questions remain unanswered in this regard.

� Dehydration. One of the more controversial factors associated with contact
lens-related dry eye is nominal water content (and refractive index) of a lens
and associated lens dehydration. The refractive index of a low water-content
contact lens is higher than that of a high water-content lens, and dehydration
results in an increase in refractive index. Generally, low water-content lenses
may lose about 1% of their water content, high water-content lenses may lose up
to about 5%.4-6 For years, clinicians have relied on the theoretical
argument that a result of pre-lens tear film evaporation was lens dehydration
with accompanying drying of the eye.

In a study of more than 350 contact lens wearers,6
my colleagues and I found that patients using lower water-content hydrogels were
less likely to have contact lens-related dry eye. However, the study did not
show that lens dehydration was related to contact lens-related dry eye. Several
smaller-scale studies7-10 have evaluated contact lens dehydration and
patients� symptoms, with varied results.

Efron and Brennan7 found that patients wearing low water-content lenses that
maintained hydration (as compared to low watercontent lenses that dehydrated)
generally reported their eyes never felt dry during lens wear. Pritchard and
colleagues9 examined dehydration of three different water-content hydrogel
lenses and the relation of this dehydration to lens movement, diameter changes
and dryness symptoms. They found no correlations between dehydration, movement,
diameter and dryness symptoms.

Fonn and colleagues10 performed a similar study, but used two groups of patients
� one with symptoms of dryness and the other without such symptoms � showing no
relationship between lens dehydration and dryness, comfort or tear film thinning
time. Thus, the evidence to date seems to suggest that although high
water-content (low refractive index) lens use may be associated with contact
lensrelated dry eye symptoms, dehydration of these lenses does not seem to be
the mechanism associated with the dry eye symptoms.

One possible explanation for this is that the polar head groups associated with
the tear film lipid molecules may be attracted to lenses of higher water content
(or silicone expression), leaving their nonpolar tails extended away from the
lens surface leading to evaporation and/or dewetting.

� Transmissibility. Another issue that isn�t well understood is the relationship
between contact lens oxygen transmissibility and contact lens-related ocular
surface symptoms (e.g., comfort, dryness). The benefits of increasing oxygen
transmissibility are numerous and well-established; however, the link to
improved comfort during lens wear appears to be elusive. This might not be
surprising; in fact, one could argue that lenses with lower oxygen
transmissibility might be more comfortable because they effectively numb the
cornea, reducing its sensitivity and increasing the patient�s tolerance.

My Australian colleagues Drs. Chantal Coles and Noel Brennan have been
painstakingly addressing the issue of the relationship between oxygen
transmissibility and comfort.11 By accumulating a large dataset
composed of several completed studies, the group retrospectively evaluated seven
lens materials (balafilcon A, etafilcon A, hioxyfilcon A, lotrafilcon B,
omafilcon A, polymacon and senofilcon A). Subjects were asked questions about
comfort, dryness and end-of-day comfort after a minimum of 1 month of wear.
While senofilcon A (a silicone hydrogel, Acuvue Oasys) generally performed best
in terms of overall comfort, it was not generally true that silicone hydrogels
themselves provided improved comfort compared to their nonsilicone hydrogel
counterparts.

Tear Film Considerations

When discussing the mechanisms of contact lens-related dry eye, it is important
to consider the relationship between three key variables: the tear film; the
contact lens; and the lens-care system. It is very difficult to localize
problems to any one of these three components, because each must perform in
concert with the others.

The tear film is a complex, thin film that protects and maintains the cornea,
allowing for good vision. The �functional unit� is normally able to tolerate
environmental stresses and demands, but a contact lens disrupts the tear film,
dividing it into two layers � the pre- and post-lens tear film. The pre-lens
tear film probably consists of the superficial lipid layer anteriorly, with a
base layer that is more aqueous. The post-lens tear film likely consists of
aqueous anteriorly with a mucin gradient near the corneal epithelium. Although
we are just starting to unravel the mysteries associated with these complex
layers, we believe they must perform the normal functions of the precorneal tear
film in order for successful contact lens wear. Current investigations are
examining the physical (thickness and structure) and biochemical compositions
(e.g., lipid components, inflammatory mediators/proteins) of these layers during
lens wear, both with and without the presence of ocular surface symptoms.

When considering the underlying causes of contact lens-related dry eye
associated with the tear film, it is important to recall the components and
their interaction with the lenses. If tear film evaporation is a component of
contact lens-related dry eye, this certainly implicates the superficial lipid
layer of the tear film, as seen in Figure 3, whose function is to prevent
evaporation of the tear film.12-14 The ionicity of the material,
lipophilic surface properties (due to silicone expression), or polarity of the
water within the material may be chemically attractive to tear film biomolecules,
such as the lipid or protein components.

Studies suggest that contact lenses with high water content dehydrate to a
greater extent than low water-content hydrogel lenses, and thinner lenses
dehydrate faster than thicker lenses, and this has been implicated as a cause of
lens-related dry eye.4,16 However, recent work suggests that while
high water-content lenses typically are associated with lens-related dry eye,
dehydration of these lenses is not. The likely explanation for this finding is
that the extra water in these materials attracts the polar components of the
tears (i.e., polar lipids or proteins), altering their surface wettability and
tear film evaporation (i.e., increased pre-lens tear film thinning and breakup).
With altered pre-lens tear film thinning, this leads to a direct increase in
osmolality (i.e., increased thinning rate reduces the volume of the solvent
present, but the solutes go unchanged), and it is likely the increase in
osmolality that leads to patient symptoms.6

However, lipid alterations or interactions with the lens may contribute only in
part to tear film evaporation. Proteins are involved in the innate defense of
the ocular surface, in addition to having scavenging or surfactant properties
themselves. Many of the proteins known to be present in the tear film (e.g.,
lysozyme, lactoferrin, albumin) have protective roles, serving as antimicrobial
agents. Another consideration is that increases in osmolality (as discussed
above) have been shown to lead to an up regulation of the stress response in
animal models.17 The stress response is usually characterized by an
expression of proteins that are involved in the inflammatory response, such as
interleukins, cytokines, matrix metalloproteinases and others. Thus, while
likely not the direct inciting factor, inflammation is likely a result of
increased evaporation/tear film thinning given the osmolality link between the
two (i.e., fast evaporation/thinning leads to increased osmolality, which leads
to the inflammatory response).

Ocular Surface Sensation

Ocular surface sensation is a complicated area of research. Contact lens wear is
associated with alterations in corneal sensation. How much the sensation is
altered relates to the oxygen transmissibility of the contact lens and the
length of wear (short-term vs. long-term).

The modulus (stiffness) of the polymer material may affect a contact lens�s
overall comfort. To my knowledge, the relationship between ocular surface
sensation and lens material modulus is not understood, although, intuitively,
one would think that a lower modulus lens might be more comfortable, while a
higher modulus lens might be easier to handle. It does appear as though some of
the more mechanical� contact lens complications (i.e., superior epithelial
arcuate lesions, contact lens-associated papillary conjunctivitis) may be
related to lens modulus and patient comfort during lens wear. One of the more
controversial topics related to patient comfort during contact lens wear is
corneal staining. In the general, non-lens wearing population, some degree of
corneal staining is somewhat common, and it typically lasts for about a day.

Care Solution Considerations

We all acknowledge that care solutions/systems have an important role in
disinfecting contact lenses. Recent events associated with product recalls
remind us that we should never take the care system for granted. It is critical
that the industry continue to focus on improving our understanding of
disinfectants used in marketed products. It is also critical that we move past
so-called incremental improvements and toward true advances and next-generation
products.

Remember, too, that care systems can improve patient comfort. Manufacturers
strive to improve comfort through the demulcents and surfactants (surface active
agents) used in their products. Demulcents, which are water-soluble polymers
such as hydroxypropyl methylcellulose, sorbitol and propylene glycol, are being
included in care systems to improve lubrication. Surfactants may improve comfort
on several fronts. First, they can help improve wetting by lowering the surface
tension of a liquid or the surface energy of a solid. Surfactants are
amphipathic (hydrophobic tails and hydrophilic heads), and because of this, many
surfactants can form micelles.The shape of a micelle is related to the pH of the
system. Micelles will form only when the surfactant�s concentration is greater
than the critical micelle concentration (CMC). When surfactants are present
above the CMC, they take on emulsification/detergent properties. In this regard,
they can help clean contact lenses by incorporating poorly soluble hydrophobic
material (i.e., proteins, etc.) in their core where they, in essence, surround
the protein and denature it. Theoretically, a cleaner lens might be associated
with improved comfort, although we do think that a biofilm is an important part
of the picture as well.

Long-standing Goal

Comfortable contact lens wear is arguably one of the biggest clinical challenges
facing eyecare practitioners today. While we have gained some insight into the
composition of the tears and the mechanisms of dry eye disease, work is still
needed to move the field ahead. We should all look forward to new products,
including polymer materials, contact lens care systems and rewetting agents that
will help our patients safely and successfully wear contact lenses.